Antibodies are molecules in the center of biological defense and have been an important tool used in research and diagnosis. In more recent years, novel therapeutic agents, i.e. antibody drugs utilizing antibodies as medicaments, have shown remarkable therapeutic effects. In order to obtain novel antibodies that can be used as medicaments and the like in a rapid and secure manner, it is required to establish a production platform by introducing novel techniques.
Many of the functional antigen epitopes of human proteins which are targeted by antibody drugs have low antigenicity in mice. Therefore, sufficient immune reaction is not triggered even when the antigens are inoculated to mice, and thus it is not easy to obtain antibodies toward such antigens with antigen epitopes having low antigenicity in mice. Therefore, there is a need for a technique that allows efficient production of antibodies in animals other than mice having high immunogenicity towards human antigens.
Meanwhile, when obtaining a recombinant monoclonal antibody from immunized animals by genetic engineering means, a method is used in which antigen specific single plasma cells are separated. Proposed methods for separating antigen specific single plasma cells include those in which an antibody secreted from the single plasma cells is used and in which an antibody expressed on the single plasma cells is used.
PTL 1 discloses a fluorescent probe for identifying or isolating plasma cells and a method for identifying or isolating plasma cells using the probe. PTL 2 discloses a method for producing an antibody with specificity toward an antigen of interest from plasma cells isolated by the method described in PTL 1.
NPL 1 discloses efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning.
NPL 2 discloses cloning and expression of murine IgGenes from single human B cells.
NPL 3 discloses rapid isolation of antigen-specific antibody-secreting cells using a chip-based immunospot array.